A stabilized HIV-1 envelope glycoprotein trimer fused to CD40 ligand targets and activates dendritic cells
Mark Melchers, Katie Matthews, Robert P de Vries, Dirk Eggink, Thijs van Montfort, Ilja Bontjer, John P Moore, Rogier W Sanders
Retrovirology | BIOMED CENTRAL LTD | Published : 2011
BACKGROUND: One reason why subunit protein and DNA vaccines are often less immunogenic than live-attenuated and whole-inactivated virus vaccines is that they lack the co-stimulatory signals provided by various components of the more complex vaccines. The HIV-1 envelope glycoprotein complex (Env) is no exception to this rule. Other factors that limit the induction of neutralizing antibodies against HIV-1 lie in the structure and instability of Env. We have previously stabilized soluble trimeric mimics of Env by introducing a disulfide bond between gp120 and gp41 and adding a trimer stabilizing mutation in gp41 (SOSIP.R6 gp140). RESULTS: We further stabilized the SOSIP.R6 gp140 using a GCN4-ba..View full abstract
Awarded by AIDS fund (Amsterdam)
We are grateful to Richard Kornbluth, William Olson, Dennis Burton and James Robinson for reagents, and PJ Klasse for helpful discussions. This research was supported in part by grants #2005021 (to BB) and #2008013 (to RWS) from the AIDS fund (Amsterdam). RWS is a recipient of Veni and Vidi fellowships from the Netherlands Organization for Scientific Research (NWO), and a Mathilde Krim research fellowship from the American Foundation for AIDS Research (amfAR).